Increased cytokine levels and abnormal response of myeloid progenitor cells to granulocyte colony-stimulating factor in a case of severe congenital neutropenia. In vitro effects of stem cell factor.

Abstract

Purpose: The cytokine levels and the in vitro granulopoiesis were studied to evaluate the mechanism of impaired granulopoiesis in severe congenital neutropenia (SCN).

Patient and methods: The patient was a 5-year-old boy with SCN. We assayed the colony-stimulating activity (CSA) produced by peripheral blood (PB) cells from the patient. The plasma levels of cytokines were measured using enzyme immunoassay. These included granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-6, and tumor necrosis factor-alpha. The effects of IL-3 and stem cell factor (SCF) on the proliferation of granulocyte-macrophage colony-forming cells (GM-CFCs) were studied.

Results: CSA produced by PB cells from the patient was almost the same as in the healthy control. The level of endogenous G-CSF was elevated to 334 pg/ml, and GM-CSF, IL-2, IL-3, and IL-6 were slightly elevated. The numbers of GM-CFCs were markedly depressed in the presence of G-CSF alone and showed no increment on additional stimulation by IL-3. SCF in combination with G-CSF significantly augmented the proliferation of GM-CFCs.

Conclusions: These findings suggest that some cytokines including G-CSF may be elevated in SCN patients and that CSF may play an important role in the pathogenesis of SCN.